Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, which leads to bone fragility and increased fracture risk. The major factor contributing to the structural deterioration of cortical bone is increased porosity caused by bone remodeling. Consequently, the strength and stiffness of bones are reduced. For prolonged bed rest, immobilization and space flight, disuse atrophy of bone is prevalent and increases fracture risk when normal bone loading is resumed. Disuse osteopenia occurs in many animals including rats, roosters, hibernating ground squirrels, sheep, dogs, monkeys and humans. On the contrary, black bears may not develop osteopenia during long periods of disuse (i.e., hibernation) to the extent that other animals do. During hibernation, osteoclastic resorption increases as it does in other animals. However, osteoblastic formation levels remain normal, a metabolic bone feature unique to bears. Additionally, black bears may have a mechanism for more rapid and complete bone recovery from disuse than other animals do. Therefore, we hypothesize that black bears minimize the degradation of bone material properties, which result from annual periods of disuse, because they maintain normal bone formation during disuse and make a rapid and complete recovery of bone mass during remobilization. The overall objective of this project is to understand the effects of annual periods of disuse on bone mechanical properties, histologic features, and mineral composition, and the biological mechanisms that may be involved in bone recovery during remobilization. The goals of the proposed project are (1) to quantify age-related changes in black bear bone mechanical properties, mineral content, and histologic features, and (2) to quantify the effects of black bear serum on mechanically stimulated intracellular calcium signaling in osteoblastic cells in vitro. This will be done with bone tissue from hunter-killed bears, and serum collected from live bears, which will be used for in vitro experiments with osteoblastic cells. The long-term impact of the proposed research includes an understanding of the biological mechanisms involved in disuse osteoporosis and advances in the treatment and prevention of osteoporosis, including the development of novel pharmaceutical therapies. Additionally, this research program is designed to train undergraduate students in the basic skills of experimental design, experimental methods, and data analysis for biological research. [unreadable] [unreadable]